As established by various studies, it is recognized that cholesterol and triglycerides play a major role in the formation of artherosclerotic plaques by accelerating the deposition of blood lipids in the arterial wall.
Very few hypolipidemic benzoic acids have been reported until recently. The most important hypolipidemic derivatives of benzoic acid disclosed to date is tibric acid. U.S. Pat. No. 3,843,662 and U.S. Pat. No. 3,855,255; see also Ryan et al. Clinc. Pharmacol. Therap., 15,218 (1974). There have been two reports of hypolipidemic activity in p-amino benzoic acid analogs. Ger. Offen. No. 2,316,914 (CA82:43070h) and Belgian Pat. No. 815,703. A number of patents have issued describing hydroxy and thio benzoic acid derivatives as hypolipidemics or for use in the treatment for heart disease. Japanese Pat. No. 7,333,742; Japanese Pat. No. 7,333,743; Ger. Offen. No. 2,311,020 (CA82:16563q); U.S. Pat. No. 3,716,644; U.S. Pat. No. 3,732,295; Japanese Pat. No. 7,368,541 (CA80:59739c); Japanese J4 No. 9,070,942; J. Pharm. Soc. Jap. 94 (3) 387-96 (1974); German Offen. No. 1,963,187 (CA75:63401a); Belgian Pat. No. 805,172; Arznei. Forsch., 22 (2) 465-8 (1972); U.S. Pat. No. 3,856,951; and German Offen. No. 2,149,070. Alkylamino benzoic acid derivatives have also been described as hypolipidemic agents. U.S. Pat. No. 3,868,416. In addition, there has been much work with somewhat related compounds having unsaturated bonds for their liquid crystal properties. Japanese Pat. No. J4 9,052,785, British Pat. No. 1,373,609, and Ger. Offen. No. 2,306,738.
Reports in the literature include p-benzylaminobenzoic acid itself. CA51:8720g; 52:18498d; 52:P8539d; 55:5867c; 57:14973e. Reported monosubstituted p-benzylaminobenzoic acids include various amino, nitro, and methoxy substitutions. CA64:60105g; CA65:7001f; CA64:20105g; and Ger. Offen. 716,668 (CA38:2345g). Several simple multi-substituted analogs have also been reported. CA52:16630b; CA48:6444h; and CA75:141136j. The esters of p-cyclohexylaminobenzoic acid are described in U.S. Pat. Nos. 2,714,607 and 2,857,417. See also CA53:5203h. No hypolipidemic activity has been mentioned for any of these compounds.
Other related art includes p(ar, .alpha.-dimethylbenzylamino)benzoic acid and a piperonyl derivative. CA38:P2346. A bicyclic derivative has also been reported. CA58:521f. Related compounds are also disclosed in U.S. Pat. Nos. 3,257,191; 3,674,843; 3,674,844 and 3,780,027.